Alcohol, tobacco, and other drug use remains highly prevalent among US adolescents and is a threat to their well-being and to the public health. Clinical trials and meta-analyses evidence supports the effectiveness of Screening, Brief Intervention and Referral to Treatment (SBIRT) for adolescents with substance misuse, and SBIRT is recommended by the American Academy of Pediatrics. Despite federal support of SBIRT, primary care providers have been slow to adopt this evidence-based approach. Thus, research is needed to determine effective ways to implement SBIRT for adolescents so that this approach can be brought to scale and achieve its full public health impact. Guided by Proctor's conceptual model of implementation research, the proposed study is a multi-site, cluster randomized trial to compare two principal strategies of SBIRT delivery within adolescent medicine. In the Generalist Strategy, the primary care provider delivers brief intervention (BI) fo substance misuse. In the Specialist Strategy, BIs are delivered by behavioral health counselors. The 8 study sites, primary care clinics operated by a large, urban Federally Qualified Health Center in Baltimore, will be randomly assigned to implement SBIRT for adolescents using either the Generalist or Specialist strategies. Staff at each site will be trained in the assigned implementation strategy, and quarterly booster trainings will be provided during the implementation period. Implementation outcomes, including: penetration, costs/cost- effectiveness, acceptability, timeliness, fidelity/adherence, and patient satisfaction will be assessed during the 18-month-long implementation period using a complementary combination of administrative service encounter data, provider and patient surveys, and qualitative interviews. At the end of the active implementation period, all training and technical support activities will cease for 12 months in order to measure relative sustainability. Specific Aims are: (1) to examine the relative effectiveness of the Generalist v. the Specialist implementation strategies in terms of penetration of (i) BI for those adolescents for whom it is indicated and (ii referral to specialty substance abuse treatment when indicated; (2) To determine the (iii) cost and (iv) cost-effectiveness of the two strategies; and (3) to compare the two strategies in terms of key implementation factors, including (v) acceptability; (vi) timeliness; (vii) fidelity/adherene; (viii) patient satisfaction; and (ix) sustainability. The proposed study is significant because it ill fill a major gap in scientific knowledge regarding the best SBIRT implementation strategy at a time when SBIRT is poised to be brought to scale under health care reform. It is innovative because it will be the first implementation study of adolescent SBIRT and one of the first prospective trials to use an implementation science conceptual framework for brief interventions. Finally, the study will include novel cost data that will provide guidance about the adoption of SBIRT in adolescent health care.